The average number of red blood cell transfusions received by patients who presented with a GIB during their hospitalization was just more than 2 units. Patients who developed GIB had approximately twice the number of transfusions in the first year after device implantation, on average, compared with patients who did not develop GIB (18.4 vs 9.3, respectively, p < 0.001).
There were no reported mortalities as a result of GIB and no surgical interventions were necessary. There was no statistical difference in 6 month, 1 year, or 2 year survival in patients who developed a GIB and those who did not (82% vs 83%, 79% vs 74%, and 67% vs 59%, respectively; log-rank p = 0.35). Kaplan-Meier survival curves for patients who developed GIB versus for those who did not are demonstrated in Figure 3.
With continued improvement in CF-LVAD technology and increasing experience with postoperative follow-up, outcomes for patients with end-stage heart failure have continued to improve.2,3,17,18 However, GIB actually appears to be increasing in incidence since the introduction of CF-LVADs,7,8,19 and has been reported to be among the most common reasons for readmission after CF-LVAD implantation.14,20,21 The etiology of GIB in CF-LVAD recipients is likely multifactorial; proposed contributing factors include the narrowed pulse pressures and shear forces inherent in CF-LVAD implantation,22,23 acquired von Willebrand syndrome caused by fragmentation of von Willebrand factor multimers,9,10,12,24,25 and impaired platelet aggregation.12,13 Our institutional experience of GIB rate compares favorably with those previously reported,7,15,19,26,27 and similar to previous series,15,28 did not impact survival.
In these patients, a multidisciplinary approach is preferred, with input from cardiology, cardiothoracic surgery, and gastroenterology. Cessation of both anticoagulation and antiplatelet therapy is the primary treatment for uncomplicated GIB in CF-LVAD patients. Durable discontinuation of anticoagulants or antiplatelet agents may even be necessary,29 but this decision must be balanced against the risk of device thrombosis.30 Ongoing studies such as TRACE (NCT01477528) are anticipated to shed further light on the risks of scaling back anticoagulant therapy after bleeding events in the HM II population.
When needed, treatment modalities include proton pump inhibitors and standard endoscopic treatment, such as epinephrine injection and clip placement. Newer treatments that have been described with varying success include systemic epinephrine or octreotide, either by infusion or by subcutaneous injection.32,33 In patients with severe or refractory GIB, long-term cessation of anticoagulation29,34 or surgical therapy35 may be required.
In our study, risk factors predicting the development of GIB included older age, lower preoperative albumin level, and lower preoperative BMI. Surprisingly, females developed GIB at approximately twice the rate of males in our cohort, although the reasons for this association remain unclear. However, this finding is consistent with a recent analysis of preoperative risk factors for postoperative nonsurgical bleeding in CF-LVAD recipients by Boyle et al,36 which demonstrated female gender to be an independent risk factor for both bleeding and stroke.
The main finding of our retrospective analysis was that the development of GIB while on CF-LVAD support negatively impacts rates of cardiac transplantation. Although the association of GIB with increased transplant waiting time is likely multifactorial, it is troubling, as the development of GIB appears to additionally increase the risk for thromboembolic events while on device support as well.28,37 In addition, increased blood transfusion rates, because of repeated bleeding episodes, can predispose to increased allosensitization, thereby decreasing the likelihood of finding a compatible organ. Previous studies have reported that the average number of blood transfusions a patient receives on readmission for a GIB-related complication is 2–4 units.7 Indeed, in our cohort, the average number of red blood cell transfusions in patients who developed a GIB was just more than 2 units. Furthermore, patients who developed GIB had nearly twice the number of transfusions in the first year after device implantation, on average, compared with patients who did not develop GIB. The risk of allosensitization caused by recent blood transfusions in these patients increases the need for prospective cross-matches, thereby limiting the donor pool for LVAD patients with a recent GI bleed. Finally, it is also possible that patients with a recent GI bleed experience delays in being reactivated on the cardiac transplantation list because of concerns of recurrent bleeding in the perioperative period as a result of the heparinization needed to perform cardiac transplantation.
This study was a retrospective chart review and with its inherent limitations that must be acknowledged. Charts were only available for review from our institution and the potential inaccuracy of data not retrievable in our electronic medical record system (e.g., at other institutions) could lead to a falsely low reported number of blood transfusions or of GIB-related episodes. In addition, some patients were not endoscopically evaluated for their GIB episodes, and no definitive, confirmatory site of GIB was found in others. Finally, the reasons why patients who developed GIB experienced longer transplant waiting times has not been definitively established. Further studies are needed to better explain this association.
In this large, single-center analysis, it was noted that although mortality did not appear to be affected by the presence or absence of GIB episodes, the rates of cardiac transplantation were significantly decreased in patients who developed GIB while on LVAD support. Although the mechanism for this association remains unclear and at best multifactorial, repeat bleeding episodes leading to increased blood transfusion rates can cause an increase in allosensitization, thereby decreasing the likelihood of finding a compatible organ on an ever-growing waiting list. An aggressive preoperative screening program of patients to determine the presence of preexisting angiodysplasias or von Willebrand syndrome (thought to be the main culprits of CF-LVAD-related GIB) could potentially allow for minimizing development of GIB postoperatively;4 however this has not been definitively demonstrated.
The authors thank Mary Knatterud, PhD, for her assistance in editing the manuscript.
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